The Experts below are selected from a list of 258024 Experts worldwide ranked by ideXlab platform
Mitja I Kurki - One of the best experts on this subject based on the ideXlab platform.
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genome wide association study of intracranial aneurysm identifies a new association on chromosome 7
Stroke, 2014Co-Authors: Tatiana Foroud, Dongbing Lai, Daniel L Koller, Femke N G Van T Hof, Mitja I Kurki, Craig S Anderson, Robert D Brown, E S ConnollyAbstract:Background and Purpose—Common variants have been identified using genome-wide association studies which contribute to intracranial aneurysms (IA) susceptibility. However, it is clear that the variants identified to date do not account for the estimated genetic contribution to disease risk. Methods—Initial analysis was performed in a discovery sample of 2617 IA cases and 2548 controls of white ancestry. Novel chromosomal regions meeting genome-wide significance were further tested for association in 2 independent replication samples: Dutch (717 cases; 3004 controls) and Finnish (799 cases; 2317 controls). A meta-analysis was performed to combine the results from the 3 studies for key chromosomal regions of interest. Results—Genome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P<1.0×10−11), in a gene previously associated with IA. A novel region on chromosome 7, near HDAC9, was associated with IA (rs10230207; P=4.14×10−8). This association replicate...
Yusuke Nakamura - One of the best experts on this subject based on the ideXlab platform.
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genome wide association study for intracranial aneurysm in the japanese population identifies three candidate susceptible loci and a functional genetic variant at ednra
Human Molecular Genetics, 2012Co-Authors: Siewkee Low, Hitoshi Zembutsu, Atsushi Takahashi, Michiaki Kubo, Naoyuki Kamatani, Pei Chieng Cha, Yusuke NakamuraAbstract:Aneurysmal subarachnoid hemorrhage (aSAH) is the most serious subtype of stroke. Genetic factors have been known to play an important role in the development of intracranial aneurysm (IA), some of which further progress to subarachnoid hemorrhage (SAH). In this study, we conducted a genome-wide association study (GWAS) to identify common genetic variants that are associated with the risk of IA, using 1383 aSAH subjects and 5484 control individuals in the Japanese population. We selected 36 single-nucleotide polymorphisms (SNPs) that showed suggestive association (P <1 × 10(-4)) in the GWAS as well as additional 7 SNPs that were previously reported to be associated with IA, and further genotyped an additional set of 1048 IA cases and 7212 controls. We identified an SNP, rs6842241, near EDNRA at chromosome 4q31.22 (combined P-value = 9.58 × 10(-9); odds ratio = 1.25), which was found to be significantly associated with IA. Additionally, we successfully replicated and validated rs10757272 on CDKN2BAS at chromosome 9p21.3 (combined P-value = 1.55 × 10(-7); odds ratio = 1.21) to be significantly associated with IA as previously reported. Furthermore, we performed functional analysis with the associated genetic variants on EDNRA, and identified two alleles of rs6841581 that have different binding affinities to a nuclear protein(s). The transcriptional activity of the susceptible allele of this variant was significantly lower than the other, suggesting that this functional variant might affect the expression of EDNRA and subsequently result in the IA susceptibility. Identification of genetic variants on EDNRA is of clinical significance probably due to its role in vessel hemodynamic stress. Our findings should contribute to a better understanding of physiopathology of IA.
Anna Maria Di Blasio - One of the best experts on this subject based on the ideXlab platform.
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an italian association study and meta analysis with previous gwas confirm wnt4 CDKN2BAS and fn1 as the first identified susceptibility loci for endometriosis
Journal of Medical Genetics, 2013Co-Authors: Luca Pagliardini, Davide Gentilini, Paola Vigano, Paola Paninabordignon, M Busacca, Massimo Candiani, Anna Maria Di BlasioAbstract:Background Although endometriosis may benefit from primary prevention measures, the epidemiological risk factors identified are equivocal. Two genome-wide association studies (GWAS) have been conducted for endometriosis in two different ethnic populations but results are still to be replicated consistently and across various ethnicities. To confirm the association of GWAS-derived susceptibility loci, we conducted a replication Italian case-control study and a meta-analysis. Methods An independent set of 305 laparoscopically-proven endometriosis patients and 2710 controls were recruited. Four SNPs— CDKN2BAS rs1333049, rs7521902 close to WNT4 , rs12700667 in an inter-genic region on 7p15.2 and fibronectin 1 rs1250248—were selected for this association study. Results Rs1333049 risk allele G frequency resulted significantly higher in endometriosis patients compared with controls (OR 1.32, 95% CI 1.11 to 1.57), confirming the role of this locus also in the Caucasian population. The meta-analysis showed that rs7521902 was associated with endometriosis at a genome-wide significance (pmeta=2.23×10−9) while for rs1250248, a genome-wide significant pmeta value of 3.89×10−9 was detected only in association with severe forms. An epistatic interaction between rs7521902 and rs1250248 (OR 1.56, p=1.19×10−2) was found especially in presence of ovarian disease (OR=2.15, p=3.12×10−4). Conclusions We confirm WNT4 , CDKN2BAS and FN1 as the first identified common loci for endometriosis.
Hitoshi Zembutsu - One of the best experts on this subject based on the ideXlab platform.
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genome wide association study for intracranial aneurysm in the japanese population identifies three candidate susceptible loci and a functional genetic variant at ednra
Human Molecular Genetics, 2012Co-Authors: Siewkee Low, Hitoshi Zembutsu, Atsushi Takahashi, Michiaki Kubo, Naoyuki Kamatani, Pei Chieng Cha, Yusuke NakamuraAbstract:Aneurysmal subarachnoid hemorrhage (aSAH) is the most serious subtype of stroke. Genetic factors have been known to play an important role in the development of intracranial aneurysm (IA), some of which further progress to subarachnoid hemorrhage (SAH). In this study, we conducted a genome-wide association study (GWAS) to identify common genetic variants that are associated with the risk of IA, using 1383 aSAH subjects and 5484 control individuals in the Japanese population. We selected 36 single-nucleotide polymorphisms (SNPs) that showed suggestive association (P <1 × 10(-4)) in the GWAS as well as additional 7 SNPs that were previously reported to be associated with IA, and further genotyped an additional set of 1048 IA cases and 7212 controls. We identified an SNP, rs6842241, near EDNRA at chromosome 4q31.22 (combined P-value = 9.58 × 10(-9); odds ratio = 1.25), which was found to be significantly associated with IA. Additionally, we successfully replicated and validated rs10757272 on CDKN2BAS at chromosome 9p21.3 (combined P-value = 1.55 × 10(-7); odds ratio = 1.21) to be significantly associated with IA as previously reported. Furthermore, we performed functional analysis with the associated genetic variants on EDNRA, and identified two alleles of rs6841581 that have different binding affinities to a nuclear protein(s). The transcriptional activity of the susceptible allele of this variant was significantly lower than the other, suggesting that this functional variant might affect the expression of EDNRA and subsequently result in the IA susceptibility. Identification of genetic variants on EDNRA is of clinical significance probably due to its role in vessel hemodynamic stress. Our findings should contribute to a better understanding of physiopathology of IA.
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a genome wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in japanese
Nature Genetics, 2010Co-Authors: Satoko Uno, Hitoshi Zembutsu, Akira Hirasawa, Atsushi Takahashi, Michiaki Kubo, Tomoko Akahane, Daisuke Aoki, Naoyuki Kamatani, Koichi HirataAbstract:Although the pathogenesis of endometriosis is not well understood, genetic factors have been considered to have critical roles in its etiology. Through a genome-wide association study and a replication study using a total of 1,907 Japanese individuals with endometriosis (cases) and 5,292 controls, we identified a significant association of endometriosis with rs10965235 (P = 5.57 x 10(-12), odds ratio = 1.44), which is located in CDKN2BAS on chromosome 9p21, encoding the cyclin-dependent kinase inhibitor 2B antisense RNA. By fine mapping, the SNP showing the strongest association was located in intron 16 of CDKN2BAS and was implicated in regulating the expression of p15, p16 and p14. A SNP, rs16826658, in the LD block including WNT4 on chromosome 1p36, which is considered to play an important role in the development of the female genital tract, revealed a possible association with endometriosis (P = 1.66 x 10(-6), odds ratio = 1.20). Our findings suggest that these regions are new susceptibility loci for endometriosis.
Atsushi Takahashi - One of the best experts on this subject based on the ideXlab platform.
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genome wide association study for intracranial aneurysm in the japanese population identifies three candidate susceptible loci and a functional genetic variant at ednra
Human Molecular Genetics, 2012Co-Authors: Siewkee Low, Hitoshi Zembutsu, Atsushi Takahashi, Michiaki Kubo, Naoyuki Kamatani, Pei Chieng Cha, Yusuke NakamuraAbstract:Aneurysmal subarachnoid hemorrhage (aSAH) is the most serious subtype of stroke. Genetic factors have been known to play an important role in the development of intracranial aneurysm (IA), some of which further progress to subarachnoid hemorrhage (SAH). In this study, we conducted a genome-wide association study (GWAS) to identify common genetic variants that are associated with the risk of IA, using 1383 aSAH subjects and 5484 control individuals in the Japanese population. We selected 36 single-nucleotide polymorphisms (SNPs) that showed suggestive association (P <1 × 10(-4)) in the GWAS as well as additional 7 SNPs that were previously reported to be associated with IA, and further genotyped an additional set of 1048 IA cases and 7212 controls. We identified an SNP, rs6842241, near EDNRA at chromosome 4q31.22 (combined P-value = 9.58 × 10(-9); odds ratio = 1.25), which was found to be significantly associated with IA. Additionally, we successfully replicated and validated rs10757272 on CDKN2BAS at chromosome 9p21.3 (combined P-value = 1.55 × 10(-7); odds ratio = 1.21) to be significantly associated with IA as previously reported. Furthermore, we performed functional analysis with the associated genetic variants on EDNRA, and identified two alleles of rs6841581 that have different binding affinities to a nuclear protein(s). The transcriptional activity of the susceptible allele of this variant was significantly lower than the other, suggesting that this functional variant might affect the expression of EDNRA and subsequently result in the IA susceptibility. Identification of genetic variants on EDNRA is of clinical significance probably due to its role in vessel hemodynamic stress. Our findings should contribute to a better understanding of physiopathology of IA.
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a genome wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in japanese
Nature Genetics, 2010Co-Authors: Satoko Uno, Hitoshi Zembutsu, Akira Hirasawa, Atsushi Takahashi, Michiaki Kubo, Tomoko Akahane, Daisuke Aoki, Naoyuki Kamatani, Koichi HirataAbstract:Although the pathogenesis of endometriosis is not well understood, genetic factors have been considered to have critical roles in its etiology. Through a genome-wide association study and a replication study using a total of 1,907 Japanese individuals with endometriosis (cases) and 5,292 controls, we identified a significant association of endometriosis with rs10965235 (P = 5.57 x 10(-12), odds ratio = 1.44), which is located in CDKN2BAS on chromosome 9p21, encoding the cyclin-dependent kinase inhibitor 2B antisense RNA. By fine mapping, the SNP showing the strongest association was located in intron 16 of CDKN2BAS and was implicated in regulating the expression of p15, p16 and p14. A SNP, rs16826658, in the LD block including WNT4 on chromosome 1p36, which is considered to play an important role in the development of the female genital tract, revealed a possible association with endometriosis (P = 1.66 x 10(-6), odds ratio = 1.20). Our findings suggest that these regions are new susceptibility loci for endometriosis.